Digital Commons Network^™

Differentially Expressed Genes In Dental Pulp Tissues Of Individuals With Symptomatic Irreversible Pulpitis With And Without History Of Covid-19, Han Na Cho, Leticia Chaves De Souza, Cleverick Johnson, John R Klein, Timothy C Kirkpatrick, Renato Silva, Ariadne Letra

Faculty, Staff and Student Publications

Introduction: Increased levels of proinflammatory markers have been reported in tissues of individuals with Coronavirus Disease 2019 (COVID-19). We hypothesize that inflamed dental pulp tissues of individuals with previous history of COVID-19 may present a differential inflammatory gene expression profile in comparison with individuals who never had COVID-19.

Materials and methods: Dental pulp tissues were collected from 27 individuals referred for endodontic treatment due to symptomatic irreversible pulpitis. Of these, 16 individuals had a history of COVID-19 (6 months to 1 year post infection) and 11 individuals had no previous history of COVID-19 (controls). Total RNA from pulp tissue samples …

Does Surgical Approach To The Hip Play A Role In Same-Day Discharge Outcomes?, Brandon Passano, Trevor Simcox, Vivek Singh, Utkarsh Anil, Ran Schwarzkopf, Roy I Davidovitch

Faculty, Staff and Student Publications

Background: Different approaches for total hip arthroplasty (THA) may offer advantages in regard to achieving same-day-discharge (SDD) success.

Methods: We retrospectively identified patients aged ≥ 18 years who underwent elective primary THA from 2015 to 2020 who were formally enrolled in a single institution's SDD program. A total of 1,127 and 207 patients underwent THA via direct anterior approach and posterior approach, respectively, were included. Cohorts were assigned based on approach. The primary outcome was failure-to-launch, defined as hospital stay extending past 1 midnight. Secondary outcomes included Forgotten Joint Score-12, Hip Disability and Osteoarthritis Outcome Score for Joint Replacement, 90-day …

A Longitudinal Investigation Of Blood Neurofilament Light Chain Levels In Chronic Cocaine Users, Francesco Bavato, Ann-Kathrin Kexel, Bruno Kluwe-Schiavon, Aleksandra Maceski, Markus R Baumgartner, Erich Seifritz, Jens Kuhle, Boris B Quednow

Faculty, Staff and Student Publications

The identification of a blood marker of brain pathology that is sensitive to substance-induced neurotoxicity and dynamically responds to longitudinal changes in substance intake would substantially improve clinical monitoring in the field of substance use and addiction. Here, we explored the hypothesis that plasma levels of neurofilament light chain (NfL), a promising marker of neuroaxonal pathology, are elevated in chronic cocaine users and longitudinally associated with changes in cocaine use. Plasma NfL levels were determined using single molecule array (SIMOA) technology at baseline and at a 4-month follow-up. Substance use was subjectively assessed with an extensive interview and objectively measured …

Disparities In The Operative Experience Between Female And Male General Surgery Residents: A Multi-Institutional Study From The Us Rope Consortium, Leah K Winer, Sarah Kader, Jonathan S Abelson, Austin C Hammaker, Chukwuma N Eruchalu, James C Etheridge, Nancy L Cho, Darci C Foote, Felicia A Ivascu, Savannah Smith, Lauren M Postlewait, Kathriena Greenwell, Katherine M Meister, Kelsey B Montgomery, Polina Zmijewski, Samuel E Byrd, Mary K Kimbrough, Stephen J Stopenski, Jeffry T Nahmias, Jalen Harvey, Deborah Farr, Zachary M Callahan, Joshua A Marks, Christopher C Stahl, Motaz Al Yafi, Jeffrey M Sutton, Ali Elsaadi, Samuel J Campbell, Shah-Jahan M Dodwad, Sasha D Adams, Matthew R Woeste, Robert C G Martin, Purvi Patel, Michael J Anstadt, Bilal Waqar Nasim, Ross E Willis, Jitesh A Patel, Melisa R Newcomb, Brian C George, Ralph C Quillin, Alexander R Cortez

Faculty, Staff and Student Publications

OBJECTIVE: To examine differences in resident operative experience between male and female general surgery residents.

BACKGROUND: Despite increasing female representation in surgery, sex and gender disparities in residency experience continue to exist. The operative volume of male and female general surgery residents has not been compared on a multi-institutional level.

METHODS: Demographic characteristics and case logs were obtained for categorical general surgery graduates between 2010 and 2020 from the US Resident OPerative Experience Consortium database. Univariable, multivariable, and linear regression analyses were performed to compare differences in operative experience between male and female residents.

RESULTS: There were 1343 graduates from …

Fast Inference Of Genetic Recombination Rates In Biobank Scale Data, Ardalan Naseri, William Yue, Shaojie Zhang, Degui Zhi

Faculty, Staff and Student Publications

Although rates of recombination events across the genome (genetic maps) are fundamental to genetic research, the majority of current studies only use one standard map. There is evidence suggesting population differences in genetic maps, and thus estimating population-specific maps, are of interest. Although the recent availability of biobank-scale data offers such opportunities, current methods are not efficient at leveraging very large sample sizes. The most accurate methods are still linkage disequilibrium (LD)-based methods that are only tractable for a few hundred samples. In this work, we propose a fast and memory-efficient method for estimating genetic maps from population genotyping data. …

Associations Between Kir/Kir-Ligand Genotypes And Clinical Outcome For Patients With Advanced Solid Tumors Receiving Bempeg Plus Nivolumab Combination Therapy In The Pivot-02 Trial, A S Feils, A K Erbe, J Birstler, K Kim, U Hoch, S L Currie, T Nguyen, D Yu, A O Siefker-Radtke, N Tannir, S M Tolaney, A Diab, P M Sondel

Faculty, Staff and Student Publications

Bempegaldesleukin (BEMPEG), a CD122-preferential IL2 pathway agonist, has been shown to induce proliferation and activation of NK cells. NK activation is dependent on the balance of inhibitory and excitatory signals transmitted by NK receptors, including Fc-gamma receptors (FCγRs) and killer immunoglobulin-like receptors (KIRs) along with their KIR-ligands. The repertoire of KIRs/KIR-ligands an individual inherits and the single-nucleotide polymorphisms (SNPs) of FCγRs can influence NK function and affect responses to immunotherapies. In this retrospective analysis of the single-arm PIVOT-02 trial, 200 patients with advanced solid tumors were genotyped for KIR/KIR-ligand gene status and FCγR SNP status and evaluated for associations with …

Dna Methylation-Based Classifier Differentiates Intrahepatic Pancreato-Biliary Tumours, Mihnea P Dragomir, Teodor G Calina, Eilís Perez, Simon Schallenberg, Meng Chen, Thomas Albrecht, Ines Koch, Peggy Wolkenstein, Benjamin Goeppert, Stephanie Roessler, George A Calin, Christine Sers, David Horst, Florian Roßner, David Capper

Faculty, Staff and Student Publications

BACKGROUND: Differentiating intrahepatic cholangiocarcinomas (iCCA) from hepatic metastases of pancreatic ductal adenocarcinoma (PAAD) is challenging. Both tumours have similar morphological and immunohistochemical pattern and share multiple driver mutations. We hypothesised that DNA methylation-based machine-learning algorithms may help perform this task.

METHODS: We assembled genome-wide DNA methylation data for iCCA (n = 259), PAAD (n = 431), and normal bile duct (n = 70) from publicly available sources. We split this cohort into a reference (n = 399) and a validation set (n = 361). Using the reference cohort, we trained three machine learning models to differentiate between these entities. Furthermore, …

Multi-Task Learning With Dynamic Re-Weighting To Achieve Fairness In Healthcare Predictive Modeling, Can Li, Sirui Ding, Na Zou, Xia Hu, Xiaoqian Jiang, Kai Zhang

Faculty, Staff and Student Publications

The emphasis on fairness in predictive healthcare modeling has increased in popularity as an approach for overcoming biases in automated decision-making systems. The aim is to guarantee that sensitive characteristics like gender, race, and ethnicity do not influence prediction outputs. Numerous algorithmic strategies have been proposed to reduce bias in prediction results, mitigate prejudice toward minority groups and promote prediction fairness. The goal of these strategies is to ensure that model prediction performance does not exhibit significant disparity among sensitive groups. In this study, we propose a novel fairness-achieving scheme based on multitask learning, which fundamentally differs from conventional fairness-achieving …

Radiomic And Deep Learning Characterization Of Breast Parenchyma On Full Field Digital Mammograms And Specimen Radiographs: A Pilot Study Of A Potential Cancer Field Effect, Natalie Baughan, Hui Li, Li Lan, Matthew Embury, Isaiah Yim, Gary J Whitman, Randa El-Zein, Isabelle Bedrosian, Maryellen L Giger

Faculty, Staff and Student Publications

PURPOSE: In women with biopsy-proven breast cancer, histologically normal areas of the parenchyma have shown molecular similarity to the tumor, supporting a potential cancer field effect. The purpose of this work was to investigate relationships of human-engineered radiomic and deep learning features between regions across the breast in mammographic parenchymal patterns and specimen radiographs.

APPROACH: This study included mammograms from 74 patients with at least 1 identified malignant tumor, of whom 32 also possessed intraoperative radiographs of mastectomy specimens. Mammograms were acquired with a Hologic system and specimen radiographs were acquired with a Fujifilm imaging system. All images were retrospectively …

Effects Of A School-Based Gardening, Cooking, And Nutrition Cluster Randomized Controlled Trial On Unprocessed And Ultra-Processed Food Consumption, Matthew R Jeans, Matthew J Landry, Sarvenaz Vandyousefi, Erin A Hudson, Marissa Burgermaster, Molly S Bray, Joya Chandra, Jaimie N Davis

Faculty, Staff and Student Publications

BACKGROUND: School-based gardening and nutrition education interventions report improvements in dietary intake, notably through fruit and vegetables. However, gardening, cooking, and nutrition randomized controlled trials are limited in evaluating dietary quality, and none have examined processed food consumption to date.

OBJECTIVES: The study examined the effects of Texas Sprouts (TX Sprouts), a gardening, cooking, and nutrition education intervention, compared with control on unprocessed and ultra-processed food (UPF) consumption in predominately low-income Hispanic children.

METHODS: TX Sprouts was a school-based cluster randomized controlled trial that consisted of 16 elementary schools randomly assigned to either the TX Sprouts intervention (n = 8 …

Who, Where, When: Colorectal Cancer Disparities By Race And Ethnicity, Subsite, And Stage, Kristin M Primm, Andrea Joyce Malabay, Taylor Curry, Shine Chang

Faculty, Staff and Student Publications

BACKGROUND: There are well-established disparities in colorectal cancer (CRC) outcomes between White and Black patients; however, assessments of CRC disparities for other racial/ethnic groups are limited.

METHODS: The Surveillance, Epidemiology, and End Results database identified patients aged 50-74 years with CRC adenocarcinoma from 2000 to 2019. Trends in age-adjusted incidence rates were computed by stage at diagnosis and subsite across five broad race/ethnic groups (White, Black, Asian/Pacific Islander [API], American Indian/Alaskan Native [AIAN], and Hispanic) and four API subgroups (East Asian, Southeast Asian, South Asian, and Pacific Islander) Multivariable logistic regression evaluated associations between race/ethnicity and diagnosis stage. Multivariable Cox …

Weakly Supervised Spatial Relation Extraction From Radiology Reports, Surabhi Datta, Kirk Roberts

Faculty, Staff and Student Publications

OBJECTIVE: Weak supervision holds significant promise to improve clinical natural language processing by leveraging domain resources and expertise instead of large manually annotated datasets alone. Here, our objective is to evaluate a weak supervision approach to extract spatial information from radiology reports.

MATERIALS AND METHODS: Our weak supervision approach is based on data programming that uses rules (or labeling functions) relying on domain-specific dictionaries and radiology language characteristics to generate weak labels. The labels correspond to different spatial relations that are critical to understanding radiology reports. These weak labels are then used to fine-tune a pretrained Bidirectional Encoder Representations from …

Effect Of Longitudinal Variation In Tumor Volume Estimation For Mri-Guided Personalization Of Breast Cancer Neoadjuvant Treatment, Natsuko Onishi, Teffany Joy Bareng, Jessica Gibbs, Wen Li, Elissa R Price, Bonnie N Joe, John Kornak, Laura J Esserman, David C Newitt, Nola M Hylton, I-Spy 2 Investigator Network

Faculty, Staff and Student Publications

Purpose To investigate the impact of longitudinal variation in functional tumor volume (FTV) underestimation and overestimation in predicting pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC). Materials and Methods Women with breast cancer who were enrolled in the prospective I-SPY 2 TRIAL (Investigation of Serial Studies to Predict Your Therapeutic Response with Imaging and Molecular Analysis 2) from May 2010 to November 2016 were eligible for this retrospective analysis. Participants underwent four MRI examinations during NAC treatment. FTV was calculated based on automated segmentation. Baseline FTV before treatment (FTV0) and the percentage of FTV change at early treatment and inter-regimen …

Minimal Positional Substring Cover Is A Haplotype Threading Alternative To Li And Stephens Model, Ahsan Sanaullah, Degui Zhi, Shaojie Zhang

Faculty, Staff and Student Publications

The Li and Stephens (LS) hidden Markov model (HMM) models the process of reconstructing a haplotype as a mosaic copy of haplotypes in a reference panel. For small panels, the probabilistic parameterization of LS enables modeling the uncertainties of such mosaics. However, LS becomes inefficient when sample size is large, because of its linear time complexity. Recently the PBWT, an efficient data structure capturing the local haplotype matching among haplotypes, was proposed to offer a fast method for giving some optimal solution (Viterbi) to the LS HMM. Previously, we introduced the minimal positional substring cover (MPSC) problem as an alternative …

Histone Demethylase Kdm5d Upregulation Drives Sex Differences In Colon Cancer, Jiexi Li, Zhengdao Lan, Wenting Liao, James W Horner, Xueping Xu, Jielin Liu, Yohei Yoshihama, Shan Jiang, Hong Seok Shim, Max Slotnik, Kyle A Labella, Chang-Jiun Wu, Kenneth Dunner, Wen-Hao Hsu, Rumi Lee, Isha Khanduri, Christopher Terranova, Kadir Akdemir, Deepavali Chakravarti, Xiaoying Shang, Denise J Spring, Y Alan Wang, Ronald A Depinho

Faculty, Staff and Student Publications

Sex exerts a profound impact on cancer incidence, spectrum and outcomes, yet the molecular and genetic bases of such sex differences are ill-defined and presumptively ascribed to X-chromosome genes and sex hormones1. Such sex differences are particularly prominent in colorectal cancer (CRC) in which men experience higher metastases and mortality. A murine CRC model, engineered with an inducible transgene encoding oncogenic mutant KRASG12D and conditional null alleles of Apc and Trp53 tumour suppressors (designated iKAP)2, revealed higher metastases and worse outcomes specifically in males with oncogenic mutant KRAS (KRAS*) CRC. Integrated cross-species molecular and transcriptomic analyses identified Y-chromosome gene histone …

Imaging In Interventional Radiology: 2043 And Beyond, Kristy K Brock, Stephen R Chen, Rahul A Sheth, Jeffrey H Siewerdsen

Faculty, Staff and Student Publications

Since its inception in the early 20th century, interventional radiology (IR) has evolved tremendously and is now a distinct clinical discipline with its own training pathway. The arsenal of modalities at work in IR includes x-ray radiography and fluoroscopy, CT, MRI, US, and molecular and multimodality imaging within hybrid interventional environments. This article briefly reviews the major developments in imaging technology in IR over the past century, summarizes technologies now representative of the standard of care, and reflects on emerging advances in imaging technology that could shape the field in the century ahead. The role of emergent imaging technologies in …

Genome-Wide Association Study Of Bladder Cancer Reveals New Biological And Translational Insights, Stella Koutros, Lambertus A Kiemeney, Parichoy Pal Choudhury, Roger L Milne, Evangelina Lopez De Maturana, Yuanqing Ye, Vijai Joseph, Oscar Florez-Vargas, Lars Dyrskjøt, Jonine Figueroa, Diptavo Dutta, Graham G Giles, Michelle A T Hildebrandt, Kenneth Offit, Manolis Kogevinas, Elisabete Weiderpass, Marjorie L Mccullough, Neal D Freedman, Demetrius Albanes, Charles Kooperberg, Victoria K Cortessis, Margaret R Karagas, Alison Johnson, Molly R Schwenn, Dalsu Baris, Helena Furberg, Dean F Bajorin, Olivier Cussenot, Geraldine Cancel-Tassin, Simone Benhamou, Peter Kraft, Stefano Porru, Angela Carta, Timothy Bishop, Melissa C Southey, Giuseppe Matullo, Tony Fletcher, Rajiv Kumar, Jack A Taylor, Philippe Lamy, Frederik Prip, Mark Kalisz, Stephanie J Weinstein, Jan G Hengstler, Silvia Selinski, Mark Harland, Mark Teo, Anne E Kiltie, Adonina Tardón, Consol Serra, Alfredo Carrato, Reina García-Closas, Josep Lloreta, Alan Schned, Petra Lenz, Elio Riboli, Paul Brennan, Anne Tjønneland, Thomas Otto, Daniel Ovsiannikov, Frank Volkert, Sita H Vermeulen, Katja K Aben, Tessel E Galesloot, Constance Turman, Immaculata De Vivo, Edward Giovannucci, David J Hunter, Chancellor Hohensee, Rebecca Hunt, Alpa V Patel, Wen-Yi Huang, Gudmar Thorleifsson, Manuela Gago-Dominguez, Pilar Amiano, Klaus Golka, Mariana C Stern, Wusheng Yan, Jia Liu, Shengchao Alfred Li, Shilpa Katta, Amy Hutchinson, Belynda Hicks, William A Wheeler, Mark P Purdue, Katherine A Mcglynn, Cari M Kitahara, Christopher A Haiman, Mark H Greene, Thorunn Rafnar, Nilanjan Chatterjee, Stephen J Chanock, Xifeng Wu, Francisco X Real, Debra T Silverman, Montserrat Garcia-Closas, Kari Stefansson, Ludmila Prokunina-Olsson, Núria Malats, Nathaniel Rothman

Faculty, Staff and Student Publications

BACKGROUND: Genomic regions identified by genome-wide association studies (GWAS) for bladder cancer risk provide new insights into etiology.

OBJECTIVE: To identify new susceptibility variants for bladder cancer in a meta-analysis of new and existing genome-wide genotype data.

DESIGN, SETTING, AND PARTICIPANTS: Data from 32 studies that includes 13,790 bladder cancer cases and 343,502 controls of European ancestry were used for meta-analysis.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSES: Log-additive associations of genetic variants were assessed using logistic regression models. A fixed-effects model was used for meta-analysis of the results. Stratified analyses were conducted to evaluate effect modification by sex and smoking status. …

Evidence Of Novel Susceptibility Variants For Prostate Cancer And A Multiancestry Polygenic Risk Score Associated With Aggressive Disease In Men Of African Ancestry, Fei Chen, Ravi K Madduri, Alex A Rodriguez, Burcu F Darst, Alisha Chou, Xin Sheng, Anqi Wang, Jiayi Shen, Edward J Saunders, Suhn K Rhie, Jeannette T Bensen, Sue A Ingles, Rick A Kittles, Sara S Strom, Benjamin A Rybicki, Barbara Nemesure, William B Isaacs, Janet L Stanford, Wei Zheng, Maureen Sanderson, Esther M John, Jong Y Park, Jianfeng Xu, Ying Wang, Sonja I Berndt, Chad D Huff, Edward D Yeboah, Yao Tettey, Joseph Lachance, Wei Tang, Christopher T Rentsch, Kelly Cho, Benjamin H Mcmahon, Richard B Biritwum, Andrew A Adjei, Evelyn Tay, Ann Truelove, Shelley Niwa, Thomas A Sellers, Kosj Yamoah, Adam B Murphy, Dana C Crawford, Alpa V Patel, William S Bush, Melinda C Aldrich, Olivier Cussenot, Gyorgy Petrovics, Jennifer Cullen, Christine M Neslund-Dudas, Mariana C Stern, Zsofia Kote-Jarai, Koveela Govindasami, Michael B Cook, Anand P Chokkalingam, Ann W Hsing, Phyllis J Goodman, Thomas J Hoffmann, Bettina F Drake, Jennifer J Hu, Jacob M Keaton, Jacklyn N Hellwege, Peter E Clark, Mohamed Jalloh, Serigne M Gueye, Lamine Niang, Olufemi Ogunbiyi, Michael O Idowu, Olufemi Popoola, Akindele O Adebiyi, Oseremen I Aisuodionoe-Shadrach, Hafees O Ajibola, Mustapha A Jamda, Olabode P Oluwole, Maxwell Nwegbu, Ben Adusei, Sunny Mante, Afua Darkwa-Abrahams, James E Mensah, Halimatou Diop, Stephen K Van Den Eeden, Pascal Blanchet, Jay H Fowke, Graham Casey, Anselm J Hennis, Alexander Lubwama, Ian M Thompson, Robin Leach, Douglas F Easton, Michael H Preuss, Ruth J Loos, Susan M Gundell, Peggy Wan, James L Mohler, Elizabeth T Fontham, Gary J Smith, Jack A Taylor, Shiv Srivastava, Rosaline A Eeles, John D Carpten, Adam S Kibel, Luc Multigner, Marie-Élise Parent, Florence Menegaux, Geraldine Cancel-Tassin, Eric A Klein, Caroline Andrews, Timothy R Rebbeck, Laurent Brureau, Stefan Ambs, Todd L Edwards, Stephen Watya, Stephen J Chanock, John S Witte, William J Blot, J Michael Gaziano, Amy C Justice, David V Conti, Christopher A Haiman

Faculty, Staff and Student Publications

BACKGROUND: Genetic factors play an important role in prostate cancer (PCa) susceptibility.

OBJECTIVE: To discover common genetic variants contributing to the risk of PCa in men of African ancestry.

DESIGN, SETTING, AND PARTICIPANTS: We conducted a meta-analysis of ten genome-wide association studies consisting of 19378 cases and 61620 controls of African ancestry.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Common genotyped and imputed variants were tested for their association with PCa risk. Novel susceptibility loci were identified and incorporated into a multiancestry polygenic risk score (PRS). The PRS was evaluated for associations with PCa risk and disease aggressiveness.

RESULTS AND LIMITATIONS: Nine …

A Radiomics Model Based On Synthetic Mri Acquisition For Predicting Neoadjuvant Systemic Treatment Response In Triple-Negative Breast Cancer, Ken-Pin Hwang, Nabil A Elshafeey, Aikaterini Kotrotsou, Huiqin Chen, Jong Bum Son, Medine Boge, Rania M Mohamed, Abeer H Abdelhafez, Beatriz E Adrada, Bikash Panthi, Jia Sun, Benjamin C Musall, Shu Zhang, Rosalind P Candelaria, Jason B White, Elizabeth E Ravenberg, Debu Tripathy, Clinton Yam, Jennifer K Litton, Lei Huo, Alastair M Thompson, Peng Wei, Wei T Yang, Mark D Pagel, Jingfei Ma, Gaiane M Rauch

Faculty, Staff and Student Publications

Purpose

To determine if a radiomics model based on quantitative maps acquired with synthetic MRI (SyMRI) is useful for predicting neoadjuvant systemic therapy (NAST) response in triple-negative breast cancer (TNBC).

Materials and Methods

In this prospective study, 181 women diagnosed with stage I–III TNBC were scanned with a SyMRI sequence at baseline and at midtreatment (after four cycles of NAST), producing T1, T2, and proton density (PD) maps. Histopathologic analysis at surgery was used to determine pathologic complete response (pCR) or non-pCR status. From three-dimensional tumor contours drawn on the three maps, 310 histogram and textural features were extracted, resulting …

Pontocerebellar Hypoplasia Associated With Parg183trp Homozygous Variant In Exosc1 Gene: A Case Report, Nadirah S Damseh, Ali N Obeidat, Khondakar Sayef Ahammed, Motee Al-Ashhab, Motee Abu Awad, Ambro Van Hoof

Faculty, Staff and Student Publications

Pontocerebellar hypoplasia (PCH) is a heterogeneous group of rare neurodegenerative disorders characterized by a wide phenotypic range including severe motor and cognitive impairments, microcephaly, distinctive facial features, and other features according to the type. Several classes of PCH1 have been linked to mutations in the evolutionarily conserved RNA exosome complex that consists of nine subunits (EXOSC1 to EXOSC9) and facilitates the degradation and processing of cytoplasmic and nuclear RNA from the 3' end. Only a single individual with an EXOSC1 mutation was reported with clinical features of PCH type 1 (PCH1F). Here, we report a 3-month-old female with PCH and …

The Clinicogenomic Landscape Of Induction Failure In Childhood And Young Adult T-Cell Acute Lymphoblastic Leukemia, David O'Connor, Jonas Demeulemeester, Lucia Conde, Amy Kirkwood, Kent Fung, Foteini Papaleonidopoulou, Gianna Bloye, Nadine Farah, Sunniyat Rahman, Jeremy Hancock, Caroline Bateman, Sarah Inglott, Jon Mee, Javier Herrero, Peter Van Loo, Anthony V Moorman, Ajay Vora, Marc R Mansour

Faculty, Staff and Student Publications

PURPOSE: Failure to respond to induction chemotherapy portends a poor outcome in childhood acute lymphoblastic leukemia (ALL) and is more frequent in T-cell ALL (T-ALL) than B-cell ALL. We aimed to address the limited understanding of clinical and genetic factors that influence outcome in a cohort of patients with T-ALL induction failure (IF).

METHODS: We studied all cases of T-ALL IF on two consecutive multinational randomized trials, UKALL2003 and UKALL2011, to define risk factors, treatment, and outcomes. We performed multiomic profiling to characterize the genomic landscape.

RESULTS: IF occurred in 10.3% of cases and was significantly associated with increasing age, …

Compensation Cycle Consistent Generative Adversarial Networks (Comp-Gan) For Synthetic Ct Generation From Mr Scans With Truncated Anatomy, Yao Zhao, He Wang, Cenji Yu, Laurence E Court, Xin Wang, Qianxia Wang, Tinsu Pan, Yao Ding, Jack Phan, Jinzhong Yang

Faculty, Staff and Student Publications

BACKGROUND: MR scans used in radiotherapy can be partially truncated due to the limited field of view (FOV), affecting dose calculation accuracy in MR-based radiation treatment planning.

PURPOSE: We proposed a novel Compensation-cycleGAN (Comp-cycleGAN) by modifying the cycle-consistent generative adversarial network (cycleGAN), to simultaneously create synthetic CT (sCT) images and compensate the missing anatomy from the truncated MR images.

METHODS: Computed tomography (CT) and T1 MR images with complete anatomy of 79 head-and-neck patients were used for this study. The original MR images were manually cropped 10-25 mm off at the posterior head to simulate clinically truncated MR images. Fifteen …

Patient-Reported Quality Of Life In Adolescents And Young Adults With Cancer Who Received Radiation Therapy, Kelsey L Corrigan, Bryce B Reeve, John M Salsman, Elizabeth J Siembida, Grace L Smith, Maria C Swartz, Kamaria L Lee, Faraz Afridi, Lauren M Andring, Andrew J Bishop, Jillian R Gunther, J Andrew Livingston, Susan K Peterson, Michael Roth

Faculty, Staff and Student Publications

BACKGROUND: Radiation therapy (RT) is a common treatment for adolescents and young adults (AYAs, 15-39 years old) with cancer; however, it may cause toxicities that affect health-related quality-of-life (HRQOL). Thus, we assessed HRQOL in AYAs before, during, and after RT.

METHODS: We identified 265 AYAs who completed HRQOL PROMIS® surveys before (n = 87), during (n = 84), or after (n = 94) RT. Higher PROMIS® score represents more of the concept. Mean scores were compared to the general US population and minimally important differences (MIDs) were used to evaluate the impact of cancer on HRQOL. Linear regression modeling was …

Effect Of Nanoparticle Loading And Magnetic Field Application On The Thermodynamic, Optical, And Rheological Behavior Of Thermoresponsive Polymer Solutions, Christopher A P Neal, Grace V Kresge, Michelle C Quan, Valeria León, Nondumiso O Chibambo, Michelle A Calabrese

Faculty, Staff and Student Publications

Although processing via external stimuli is a promising technique to tune the structure and properties of polymeric materials, the impact of magnetic fields on phase transitions in thermoresponsive polymer solutions is not well-understood. As nanoparticle (NP) addition is also known to impact these thermodynamic and optical properties, synergistic effects from combining magnetic fields with NP incorporation provide a novel route for tuning material properties. Here, the thermodynamic, optical, and rheological properties of aqueous poly(N-isopropyl acrylamide) (PNIPAM) solutions are examined in the presence of hydrophilic silica NPs and magnetic fields, individually and jointly, via Fourier-transform infrared spectroscopy (FTIR), magneto-turbidimetry, differential scanning …

Bladder-Sparing Treatment In Patients With Bacillus Calmette-Guerin-Unresponsive Non-Muscle-Invasive Bladder Cancer: An Analysis Of Long-Term Survival Outcomes, Wei Shen Tan, Valentina Grajales, Roberto Contieri, Patrick Hensley, Kelly Bree, Pavlos Msaouel, Charles C Guo, Graciela M Nogueras-Gonzalez, Neema Navai, Colin P Dinney, Ashish M Kamat

Faculty, Staff and Student Publications

BACKGROUND: Data for bladder-sparing treatment (BST) in bacillus Calmette-Guerin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC) patients report short-term outcomes limited to 1-2 yr.

OBJECTIVE: To assess long-term survival outcomes of BCG-unresponsive NMIBC patients treated with BST.

DESIGN SETTING AND PARTICIPANTS: BCG-unresponsive NMIBC patients diagnosed between January 2000 and September 2021 from an institutional NMIBC registry were evaluated.

INTERVENTION: Long-term survival outcomes for patients receiving BST, early radical cystectomy (RC), and delayed RC were compared.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoints were overall survival (OS) and cancer-specific survival (CSS).

RESULTS AND LIMITATIONS: In total, 114 patients with a median follow-up …

Estrogen-Related Receptor Signaling In Skeletal Muscle Fitness, Danesh Sopariwala, Hao Nguyen, Vihang Narkar

Faculty, Staff and Student Publications

Skeletal muscle is a highly plastic tissue that can alter its metabolic and contractile features, as well as regenerative potential in response to exercise and other conditions. Multiple signaling factors including metabolites, kinases, receptors, and transcriptional factors have been studied in the regulation of skeletal muscle plasticity. Recently, estrogen-related receptors (ERRs) have emerged as a critical transcriptional hub in control of skeletal muscle homeostasis. ERRα and ERRγ - the two highly expressed ERR sub-types in the muscle respond to various extracellular cues such as exercise, hypoxia, fasting and dietary factors, in turn regulating gene expression in the skeletal muscle. On …

Genome-Wide Association Analysis Identifies Ancestry-Specific Genetic Variation Associated With Acute Response To Metformin And Glipizide In Sugar-Mgh, Josephine H Li, Laura N Brenner, Varinderpal Kaur, Katherine Figueroa, Philip Schroeder, Alicia Huerta-Chagoya, Miriam S Udler, Aaron Leong, Josep M Mercader, Jose C Florez

Faculty, Staff and Student Publications

AIMS/HYPOTHESIS: Characterisation of genetic variation that influences the response to glucose-lowering medications is instrumental to precision medicine for treatment of type 2 diabetes. The Study to Understand the Genetics of the Acute Response to Metformin and Glipizide in Humans (SUGAR-MGH) examined the acute response to metformin and glipizide in order to identify new pharmacogenetic associations for the response to common glucose-lowering medications in individuals at risk of type 2 diabetes.

METHODS: One thousand participants at risk for type 2 diabetes from diverse ancestries underwent sequential glipizide and metformin challenges. A genome-wide association study was performed using the Illumina Multi-Ethnic Genotyping …

Interactive Associations Of Eczema With Glutathione S-Transferase Genes In Relation To Autism Spectrum Disorder And Its Severity In Jamaican Children, Sepideh Saroukhani, Maureen Samms-Vaughan, Jan Bressler, Minjae Lee, Courtney Byrd-Williams, Manouchehr Hessabi, Megan L Grove, Sydonnie Shakespeare-Pellington, Katherine A Loveland, Mohammad H Rahbar

Faculty, Staff and Student Publications

BACKGROUND: Comorbidity of eczema with autism spectrum disorder (ASD) is increasing. We investigated the associations of eczema and its possible interaction with polymorphisms in glutathione S-transferase (GST) genes in relation to ASD and ASD severity.

METHOD: Using data from 344 1:1 age- and sex-matched ASD cases and typically developing controls, we assessed additive and interactive associations of eczema with GST genes in relation to ASD by applying conditional logistic regression models, and in relation to ASD severity in ASD cases as measured by the Autism Diagnostic Observation Schedule-2nd Edition (ADOS-2) total and domain-specific comparison scores (CSs) by fitting general linear …

Plasma Cell Myeloma With Ras/Braf Mutations Is Frequently Associated With A Complex Karyotype, Advanced Stage Disease, And Poorer Prognosis, Nianyi Li, Pei Lin, Zhuang Zuo, M James You, Wen Shuai, Robert Orlowski, Elisabet E Manasanch, Shaoying Li, Jie Xu, Sofia Garces, Fatima Zahra Jelloul, Zhenya Tang, Wei Wang, L Jeffrey Medeiros, C Cameron Yin

Faculty, Staff and Student Publications

BACKGROUND: Mutations in the RAS-MAPK pathway, such as KRAS, NRAS, and BRAF, are known as high-risk factors associated with poor prognosis in patients with various cancers, but studies in myeloma have yielded mixed results.

METHODS: We describe the clinicopathologic, cytogenetic, molecular features, and outcomes of 68 patients with RAS/BRAF-mutated myeloma, and compare with 79 patients without any mutations.

RESULTS: We show that KRAS, NRAS, and BRAF were mutated in 16%, 11%, and 5% of cases, respectively. RAS/BRAF-mutated patients had lower hemoglobin and platelet counts, higher levels of serum lactate dehydrogenase and calcium, higher percentage of bone marrow plasma cells, and …

Parametric Delineation Uncertainties Contouring (Pduc) Modeling On Ct Scans Of Prostate Cancer Patients, Vi Ly, Lizhong Liu, Carlos Cardenas, Sean Maroongroge, Brian De, Daniel El Basha, Laurence Court, Xi Luo

Faculty, Staff and Student Publications

PURPOSE: Variability in contouring contributes to large variations in radiation therapy planning and treatment outcomes. The development and testing of tools to automatically detect contouring errors require a source of contours that includes well-understood and realistic errors. The purpose of this work was to develop a simulation algorithm that intentionally injects errors of varying magnitudes into clinically accepted contours and produces realistic contours with different levels of variability.

METHODS: We used a dataset of CT scans from 14 prostate cancer patients with clinician-drawn contours of the regions of interest (ROI) of the prostate, bladder, and rectum. Using our newly developed …